Neovascularization of ischemic wounds, limb, myocardium, dental pulp and neural tissue is a vital treatment modality to prevent hypoxia, apoptosis and tissue necrosis while augmenting tissue regeneration. Current techniques to achieve blood vessel growth (angiogenesis) have focused on: i) modulating inflammation using cytokines (eg. IL-4, IL-10, MCP-1) to promote a proangiogenic M2 macrophage phenotype; ii) injecting a host of growth factors (eg. P1GF, FGF, EGF, VEGF); iii) mesenchymal stem cell transplantation; and iv) gene therapy for the induction of VEGF production. These therapies to achieve neovascularization have been hampered by low gene uptake, neoplasticity, immune rejection and maladaptive inflammatory responses. Clinical trials have been met with modest success and have failed to fully functionally recover ischemic tissue. Treatment with vascular endothelial growth factor (VEGF) has resulted in modest reversal of ischemia with much of the non-sequestered growth factor diffusing into the lymphatic system.
Promotion of angiogenesis can be stimulated by a host of factors as detailed above. However, current techniques result in small nascent vessels that either fail to anastomose with host vasculature, are immature lacking supporting pericytes, or resorb too quickly over a less than 1 week period. In coming to the present invention, three vital criteria were identified for the development of a proangiogenic material: 1) retention of vessels for long 1-2 week periods; 2) development of mature stable vessels that have a pericyte/muscular wall; and 3) efficient resorption after functional recovery. To date, the therapeutic approaches described above have failed to demonstrate success on all three criteria.